Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway

Human Molecular Genetics

Volumn 18, Issue 23, 2009, Pages 4677-4687

  Hazra, Aditi ^a,b   Kraft, Peter ^a   Lazarus, Ross ^b,c   Chen, Constance ^a   Chanock, Stephen J ^d   Jacques, Paul ^e   Selhub, Jacob ^e   Hunter, David J ^a,b  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

^e TUFTS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ALANINE; CARBON; CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; PYRIDOXAL 5 PHOSPHATE; VALINE;

ADULT; ARTICLE; CARBON METABOLISM; CHROMOSOME 10P; CHROMOSOME 16P; CHROMOSOME 19Q; CHROMOSOME 1P; CHROMOSOME 9Q; CHROMOSOME ANALYSIS; CONTROLLED STUDY; FEMALE; FOLIC ACID BLOOD LEVEL; GENE FUNCTION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC ASSOCIATION; GENETIC IDENTIFICATION; GENETIC VARIABILITY; HUMAN; MALE; NONSENSE MUTATION; PREDICTION; PRIORITY JOURNAL; SEX DIFFERENCE; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; CHROMOSOMES, HUMAN; DNA-BINDING PROTEINS; FEMALE; FOLIC ACID; GENOME-WIDE ASSOCIATION STUDY; HOMOCYSTEINE; HUMANS; MALE; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; TRANSCRIPTION FACTORS; VITAMIN B 12;

EID: 70449553669     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddp428     Document Type: Article

References (98)

1. Kim, Y.I. (2004) Folate and DNA methylation: A mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol. Biomarkers Prev., 13, 511-519.
2. Kim, Y.I. (2005) Nutritional epigenetics: Impact of folate deficiency on DNA methylation and colon cancer susceptibility. J. Nutr., 135 2703-2709.
3. Bates, C.J., Pentieva, K.D., Prentice, A., Mansoor, M.A. and Finch, S. (1999) Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over. Br. J. Nutr., 81 191-201.
4. Selhub, J. and Miller, J.W. (1992) The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am. J. Clin. Nutr., 55, 131-138.
5. Selhub, J. (2002) Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J. Nutr. Health Aging, 6, 39-42.
6. Selhub, J. (1999) Homocysteine metabolism. Annu. Rev. Nutr., 19 217-246.
7. Clayton, P.T. (2006) B6-responsive disorders: A model of vitamin dependency. J. Inherit. Metab. Dis., 29, 317-326.
8. Bender, D.A. (1994) Novel functions of vitamin B6. Proc. Nutr. Soc. 53, 625-630.
9. Watanabe, F. (2007) Vitamin B12 sources and bioavailability. Exp. Biol. Med. (Maywood), 232, 1266-1274.
10. Clarke, R., Daly, L., Robinson, K., Naughten, E., Cahalane, S., Fowler, B. and Graham, I. (1991) Hyperhomocysteinemia: An independent risk factor for vascular disease. N. Engl. J. Med., 324, 1149-1155.
11. Stampfer, M.J., Malinow, M.R., Willett, W.C., Newcomer, L.M., Upson, B., Ullmann, D., Tishler, P.V. and Hennekens, C.H. (1992) A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA, 268, 877-881.
12. Selhub, J., Jacques, P.F., Bostom, A.G., D'Agostino, R.B., Wilson, P.W., Belanger, A.J., O'Leary, D.H., Wolf, P.A., Schaefer, E.J. and Rosenberg, I.H. (1995) Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N. Engl. J. Med., 332, 286-291.
13. Perry, I.J., Refsum, H., Morris, R.W., Ebrahim, S.B., Ueland, P.M. and Shaper, A.G. (1995) Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 346, 1395-1398.
14. Mayer, E.L., Jacobsen, D.W. and Robinson, K. (1996) Homocysteine and coronary atherosclerosis. J. Am. Coll. Cardiol., 27, 517-527.
15. Ridker, P.M., Shih, J., Cook, T.J., Clearfield, M., Downs, J.R., Pradhan, A.D., Weis, S.E. and Gotto, A.M. Jr (2002) Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events. Circulation, 105, 1776-1779.
16. Selhub, J. (2006) The many facets of hyperhomocysteinemia: Studies from the Framingham cohorts. J. Nutr., 136, 1726S-1730S.
17. Bird, C.L., Swendseid, M.E., Witte, J.S., Shikany, J.M., Hunt, I.F., Frankl, H.D., Lee, E.R., Longnecker, M.P. and Haile, R.W. (1995) Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps. Cancer Epidemiol. Biomarkers Prev., 4, 709-714.
18. Giovannucci, E., Stampfer, M.J., Colditz, G.A., Rimm, E.B., Trichopoulos, D., Rosner, B.A., Speizer, F.E. and Willett, W.C. (1993) Folate, methionine, and alcohol intake and risk of colorectal adenoma. J. Natl Cancer Inst., 85, 875-884.
19. Tseng, M., Murray, S.C., Kupper, L.L. and Sandler, R.S. (1996) Micronutrients and the risk of colorectal adenomas. Am. J. Epidemiol. 144, 1005-1014.
20. Giovannucci, E., Stampfer, M.J., Colditz, G.A., Hunter, D.J., Fuchs, C., Rosner, B.A., Speizer, F.E. and Willett, W.C. (1998) Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann. Intern. Med., 129, 517-524.
21. Andres, E., Federici, L., Affenberger, S., Vidal-Alaball, J., Loukili, N.H., Zimmer, J. and Kaltenbach, G. (2007) B12 deficiency: A look beyond pernicious anemia. J. Fam. Pract., 56, 537-542.
22. Hall, C.A. and Finkler, A.E. (1966) Measurement of the amounts of the individual vitamin B12 binding proteins in plasma. II. Abnormalities in leukemia and pernicious anemia. Blood, 27, 618-622.
23. Klerk, M., Verhoef, P., Clarke, R., Blom, H.J., Kok, F.J. and Schouten, E.G. (2002) MTHFR 677C->T polymorphism and risk of coronary heart disease: A meta-analysis. JAMA, 288, 2023-2031.
24. van Oijen, M.G., Vlemmix, F., Laheij, R.J., Paloheimo, L., Jansen, J.B. and Verheugt, F.W. (2007) Hyperhomocysteinaemia and vitamin B12 deficiency: The long-term effects in cardiovascular disease. Cardiology, 107, 57-62.
25. Dhonukshe-Rutten, R.A., de Vries, J.H., de Bree, A., van der Put, N., van Staveren, W.A. and de Groot, L.C. (2009) Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations. Eur. J. Clin. Nutr. 63, 18-30.
26. Dahlin, A.M., Van Guelpen, B., Hultdin, J., Johansson, I., Hallmans, G. and Palmqvist, R. (2008) Plasma vitamin B12 concentrations and the risk of colorectal cancer: A nested case-referent study. Int. J. Cancer 122, 2057-2061.
27. Zhang, S.M., Willett, W.C., Selhub, J., Hunter, D.J., Giovannucci, E.L., Holmes, M.D., Colditz, G.A. and Hankinson, S.E. (2003) Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J. Natl Cancer Inst., 95, 373-380.
28. Hultdin, J., Van Guelpen, B., Bergh, A., Hallmans, G. and Stattin, P. (2005) Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: A prospective study. Int. J. Cancer, 113, 819-824.
29. Xu, X. and Chen, J. (2009) One-carbon metabolism and breast cancer: An epidemiological perspective. J. Genet. Genomics, 36, 203-214.
30. Galvan-Portillo, M.V., Cantoral, A., Onate-Ocana, L.F., Chen, J., Herrera-Goepfert, R., Torres-Sanchez, L., Hernandez-Ramirez, R.U., Palma-Coca, O. and Lopez-Carrillo, L. (2009) Gastric cancer in relation to the intake of nutrients involved in one-carbon metabolism among MTHFR 677 TT carriers. Eur. J. Nutr., 48, 269-276.
31. Johansson, M., Van Guelpen, B., Vollset, S.E., Hultdin, J., Bergh, A., Key, T., Midttun, O., Hallmans, G., Ueland, P.M. and Stattin, P. (2009) One-carbon metabolism and prostate cancer risk: Prospective investigation of seven circulating B vitamins and metabolites. Cancer Epidemiol. Biomarkers Prev., 18, 1538-1543.
32. Maruti, S.S., Ulrich, C.M. and White, E. (2009) Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk. Am. J. Clin. Nutr., 89, 624-633.
33. Clarke, R., Smith, A.D., Jobst, K.A., Refsum, H., Sutton, L. and Ueland, P.M. (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch. Neurol., 55, 1449-1455.
34. Kang, J.H., Irizarry, M.C. and Grodstein, F. (2006) Prospective study of plasma folate, vitamin B12, and cognitive function and decline. Epidemiology, 17, 650-657.
35. Selhub, J., Morris, M.S., Jacques, P.F. and Rosenberg, I.H. (2009) Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency. Am. J. Clin. Nutr., 89, 702S-706S.
36. Lee, J.E., Li, H., Giovannucci, E., Lee, I.M., Selhub, J., Stampfer, M. and Ma, J. (2009) Prospective study of plasma vitamin B6 and risk of colorectal cancer in men. Cancer Epidemiol. Biomarkers Prev., 18, 1197-1202.
37. Wei, E.K., Giovannucci, E., Selhub, J., Fuchs, C.S., Hankinson, S.E. and Ma, J. (2005) Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women. J. Natl Cancer Inst., 97, 684-692.
38. Vermeulen, S.H., van der Vleuten, G.M., de Graaf, J., Hermus, A.R., Blom, H.J., Stalenhoef, A.F. and den Heijer, M. (2006) A genome-wide linkage scan for homocysteine levels suggests three regions of interest. J. Thromb. Haemost., 4, 1303-1307.
39. Cesari, M., Burlina, A.B., Narkiewicz, K., Sartori, M.T., Sacchetto, A. and Rossi, G.P. (2000) Are fasting plasma homocyst(e)ine levels heritable? A study of normotensive twins. J. Investig. Med., 48 351-358.
40. den Heijer, M., Graafsma, S., Lee, S.Y., van Landeghem, B., Kluijtmans, L., Verhoef, P., Beaty, T.H. and Blom, H. (2005) Homocysteine levels - before and after methionine loading - in 51 Dutch families. Eur. J. Hum. Genet., 13, 753-762.
41. Jee, S.H., Song, K.S., Shim, W.H., Kim, H.K., Suh, I., Park, J.Y., Won, S.Y. and Beaty, T.H. (2002) Major gene evidence after MTHFR-segregation analysis of serum homocysteine in families of patients undergoing coronary arteriography. Hum. Genet., 111, 128-135.
42. Kullo, I.J., Ding, K., Boerwinkle, E., Turner, S.T., Mosley, T.H. Jr, Kardia, S.L. and de Andrade, M. (2006) Novel genomic loci influencing plasma homocysteine levels. Stroke, 37, 1703-1709.
43. Siva, A., De Lange, M., Clayton, D., Monteith, S., Spector, T. and Brown, M.J. (2007) The heritability of plasma homocysteine, and the influence of genetic variation in the homocysteine methylation pathway. QJM, 100, 495-499.
44. Hubner, R.A. and Houlston, R.S. (2007) MTHFR C677T and colorectal cancer risk: A meta-analysis of 25 populations. Int. J. Cancer, 120 1027-1035.
45. Larsson, S.C., Giovannucci, E. and Wolk, A. (2007) Folate and risk of breast cancer: A meta-analysis. J. Natl Cancer Inst., 99, 64-76.
46. Shan, X., Wang, L., Hoffmaster, R. and Kruger, W.D. (1999) Functional characterization of human methylenetetrahydrofolate reductase in Saccharomyces cerevisiae. J. Biol. Chem., 274, 32613-32618.
47. Goyette, P. and Rozen, R. (2000) The thermolabile variant 677C->T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase. Hum. Mutat., 16, 132-138.
48. Hazra, A., Kraft, P., Selhub, J., Giovannucci, E.L., Thomas, G., Hoover, R.N., Chanock, S.J. and Hunter, D.J. (2008) Common variants of FUT2 are associated with plasma vitamin B12 levels. Nat. Genet., 40, 1160-1162.
49. Tanaka, T., Scheet, P., Giusti, B., Bandinelli, S., Piras, M.G., Usala, G., Lai, S., Mulas, A., Corsi, A.M., Vestrini, A. et al. (2009) Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations. Am. J. Hum. Genet., 84, 477-482.
50. Pe'er, I., Yelensky, R., Altshuler, D. and Daly, M.J. (2008) Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet. Epidemiol., 32, 381-385.
51. Weir, B.S. (1996) Genetic Data Analysis II: Methods for Discrete Population Genetic Data. Sinauer Associates, Inc, Sunderland, MA.
52. Paré, G., Chasman, D.I., Parker, A.N., Zee, R.R.Y., Mälarstig, A., Seedorf, U., Collins, R., Watkins, H., Hamsten, A., Miletich, J.P. et al. (2009) Novel Associations of CPS1, MUT, NOX4 and DPEP1 With Plasma Homocysteine in a Healthy Population: A Genome-Wide Evaluation of 13 974 Participants in the Women's Genome Health Study. Circ. Cardiovasc. Genet., 2, 142-150.
53. Yang, Q.H., Botto, L.D., Gallagher, M., Friedman, J.M., Sanders, C.L., Koontz, D., Nikolova, S., Erickson, J.D. and Steinberg, K. (2008) Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: Findings from the third National Health and Nutrition Examination Survey DNA Bank. Am. J. Clin. Nutr., 88, 232-246.
54. Kim, Y.I. (2003) Role of folate in colon cancer development and progression. J. Nutr., 133, 3731S-3739S.
55. Frosst, P., Blom, H.J., Milos, R., Goyette, P., Sheppard, C.A., Matthews, R.G., Boers, G.J., den Heijer, M., Kluijtmans, L.A., van den Heuvel, L.P. et al. (1995) A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat. Genet., 10, 111-113.
56. Jacques, P.F., Bostom, A.G., Williams, R.R., Ellison, R.C., Eckfeldt, J.H., Rosenberg, I.H., Selhub, J. and Rozen, R. (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation, 93, 7-9.
57. Sun, D., Huang, W., Hwang, Y.Y., Zhang, Y., Zhang, Q. and Li, M.D. (2007) Regulation by nicotine of Gpr51 and Ntrk2 expression in various rat brain regions. Neuropsychopharmacology, 32, 110-116.
58. Refsum, H., Nurk, E., Smith, A.D., Ueland, P.M., Gjesdal, C.G., Bjelland, I., Tverdal, A., Tell, G.S., Nygard, O. and Vollset, S.E. (2006) The Hordaland Homocysteine Study: A community-based study of homocysteine, its determinants, and associations with disease. J. Nutr., 136, 1731S-1740S.
59. Stein, J.H., Bushara, M., Bushara, K., McBride, P.E., Jorenby, D.E. and Fiore, M.C. (2002) Smoking cessation, but not smoking reduction, reduces plasma homocysteine levels. Clin. Cardiol., 25, 23-26.
60. Jacques, P.F., Bostom, A.G., Wilson, P.W., Rich, S., Rosenberg, I.H. and Selhub, J. (2001) Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am. J. Clin. Nutr. 73, 613-621.
61. Targher, G., Bertolini, L., Zenari, L., Cacciatori, V., Muggeo, M., Faccini, G. and Zoppini, G. (2000) Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes. Diabetes Care, 23, 524-528.
62. Nygard, O., Vollset, S.E., Refsum, H., Stensvold, I., Tverdal, A., Nordrehaug, J.E., Ueland, M. and Kvale, G. (1995) Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA, 274, 1526-1533.
63. Ogasawara, M., Matsubara, Y., Mikami, H. and Narisawa, K. (1994) Identification of two novel mutations in the methylmalonyl-CoA mutase gene with decreased levels of mutant mRNA in methylmalonic acidemia. Hum. Mol. Genet., 3, 867-872.
64. Thoma, N.H. and Leadlay, P.F. (1996) Homology modeling of human methylmalonyl-CoA mutase: A structural basis for point mutations causing methylmalonic aciduria. Protein Sci., 5, 1922-1927.
65. Mikami, H., Ogasawara, M., Matsubara, Y., Kikuchi, M., Miyabayashi, S., Kure, S. and Narisawa, K. (1999) Molecular analysis of methylmalonyl-CoA mutase deficiency: Identification of three missense mutations in mut0 patients. J. Hum. Genet., 44, 35-39.
66. Acquaviva, C., Benoist, J.F., Pereira, S., Callebaut, I., Koskas, T., Porquet, D. and Elion, J. (2005) Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: Identification of 29 novel mutations in the MUT gene. Hum. Mutat., 25, 167-176.
67. Drennan, C.L., Matthews, R.G., Rosenblatt, D.S., Ledley, F.D., Fenton, W.A. and Ludwig, M.L. (1996) Molecular basis for dysfunction of some mutant forms of methylmalonyl-CoA mutase: Deductions from the structure of methionine synthase. Proc. Natl Acad. Sci. USA, 93, 5550-5555.
68. Ledley, F.D., Crane, A.M. and Lumetta, M. (1990) Heterogeneous alleles and expression of methylmalonyl CoA mutase in mut methylmalonic acidemia. Am. J. Hum. Genet., 46, 539-547.
69. Dixon, A.L., Liang, L., Moffatt, M.F., Chen, W., Heath, S., Wong, K.C., Taylor, J., Burnett, E., Gut, I., Farrall, M. et al. (2007) A genome-wide association study of global gene expression. Nat. Genet. 39, 1202-1207.
70. Aminoff, M., Carter, J.E., Chadwick, R.B., Johnson, C., Grasbeck, R., Abdelaal, M.A., Broch, H., Jenner, L.B., Verroust, P.J., Moestrup, S.K. et al. (1999) Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. Nat. Genet., 21, 309-313.
71. Goll, M.G., Kirpekar, F., Maggert, K.A., Yoder, J.A., Hsieh, C.L., Zhang, X., Golic, K.G., Jacobsen, S.E. and Bestor, T.H. (2006) Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science, 311, 395-398.
72. Franke, B., Vermeulen, S.H., Steegers-Theunissen, R.P., Coenen, M.J., Schijvenaars, M.M., Scheffer, H., den Heijer, M. and Blom, H.J. (2009) An association study of 45 folate-related genes in spina bifida: involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1). Birth Defects Res. A Clin. Mol. Teratol., 85, 216-226.
73. Johnston, J., Yang-Feng, T. and Berliner, N. (1992) Genomic structure and mapping of the chromosomal gene for transcobalamin I (TCN1): comparison to human intrinsic factor. Genomics, 12, 459-464.
74. Kelly, R.J., Rouquier, S., Giorgi, D., Lennon, G.G. and Lowe, J.B. (1995) Sequence and expression of a candidate for the human Secretor blood group alpha(1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J. Biol. Chem., 270, 4640-4649.
75. van Oijen, M.G., Laheij, R.J., de Jong, C.A., Peters, W.H. and Jansen, J.B. (2004) Vitamin B12 status and its association with Helicobacter pylori infection in alcohol dependent patients. J. Nutr. Sci. Vitaminol. (Tokyo), 50, 305-308.
76. Dholakia, K.R., Dharmarajan, T.S., Yadav, D., Oiseth, S., Norkus, E.P. and Pitchumoni, C.S. (2005) Vitamin B12 deficiency and gastric histopathology in older patients. World J. Gastroenterol., 11 7078-7083.
77. Annibale, B., Capurso, G. and Delle Fave, G. (2002) Consequences of Helicobacter pylori infection on the absorption of micronutrients. Dig. Liver Dis., 34 (Suppl. 2), S72-S77.
78. Tamura, A., Fujioka, T. and Nasu, M. (2002) Relation of Helicobacter pylori infection to plasma vitamin B12, folic acid, and homocysteine levels in patients who underwent diagnostic coronary arteriography. Am. J. Gastroenterol., 97, 861-866.
79. Kaptan, K., Beyan, C., Ural, A.U., Cetin, T., Avcu, F., Gulsen, M., Finci, R. and Yalcin, A. (2000) Helicobacter pylori - is it a novel causative agent in Vitamin B12 deficiency? Arch. Intern. Med., 160, 1349-1353.
80. Whyte, M.P., Mahuren, J.D., Fedde, K.N., Cole, F.S., McCabe, E.R. and Coburn, S.P. (1988) Perinatal hypophosphatasia: Tissue levels of vitamin B6 are unremarkable despite markedly increased circulating concentrations of pyridoxal-5′-phosphate. Evidence for an ectoenzyme role for tissue-nonspecific alkaline phosphatase. J. Clin. Invest. 81, 1234-1239.
81. Whyte, M.P., Mahuren, J.D., Vrabel, L.A. and Coburn, S.P. (1985) Markedly increased circulating pyridoxal-50-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. J. Clin. Invest., 76, 752-756.
82. Anderson, B.B., O'Brien, H., Griffin, G.E. and Mollin, D.L. (1980) Hydrolysis of pyridoxal-5′-phosphate in plasma in conditions with raised alkaline phosphate. Gut, 21, 192-194.
83. McDowell, M.A., Lacher, D.A., Pfeiffer, C.M., Mulinare, J., Picciano, M.F., Rader, J.I., Yetley, E.A., Kennedy-Stephenson, J. and Johnson, C.L. (2008) Blood folate levels: The latest NHANES results. NCHS Data Brief, 6, 1-8.
84. Selhub, J., Jacques, P.F., Bostom, A.G., Wilson, P.W. and Rosenberg, I.H. (2000) Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification. Public Health Rev., 28, 117-145.
85. Hunter, D.J., Kraft, P., Jacobs, K.B., Cox, D.G., Yeager, M., Hankinson, S.E., Wacholder, S., Wang, Z., Welch, R., Hutchinson, A. et al. (2007) A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat. Genet., 39, 870-874.
86. Kannel, W.B. (2000) The Framingham Study: ITS 50-year legacy and future promise. J Atheroscler. Thromb., 6, 60-66.
87. Herbert, A., Lenburg, M.E., Ulrich, D., Gerry, N.P., Schlauch, K. and Christman, M.F. (2007) Open-access database of candidate associations from a genome-wide SNP scan of the Framingham Heart Study. Nat. Genet., 39, 135-136.
88. Dehghan, A., Kottgen, A., Yang, Q., Hwang, S.J., Kao, W.L., Rivadeneira, F., Boerwinkle, E., Levy, D., Hofman, A., Astor, B.C. et al. (2008) Association of three genetic loci with uric acid concentration and risk of gout: A genome-wide association study. Lancet, 372 1953-1961.
89. Wilk, J.B., Chen, T.H., Gottlieb, D.J., Walter, R.E., Nagle, M.W., Brandler, B.J., Myers, R.H., Borecki, I.B., Silverman, E.K., Weiss, S.T. et al. (2009) A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet., 5 e1000429.
90. Araki, A. and Sako, Y. (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J. Chromatogr., 422, 43-52.
91. Price, A.L., Patterson, N.J., Plenge, R.M., Weinblatt, M.E., Shadick, N.A. and Reich, D. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet., 38, 904-909.
92. Lettre, G., Lange, C. and Hirschhorn, J.N. (2007) Genetic model testing and statistical power in population-based association studies of quantitative traits. Genet. Epidemiol., 31, 358-362.
93. de Bakker, P.I., Ferreira, M.A., Jia, X., Neale, B.M., Raychaudhuri, S. and Voight, B.F. (2008) Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum. Mol. Genet. 17, R122-R128.
94. Higgins, J.P. and Thompson, S.G. (2002) Quantifying heterogeneity in a meta-analysis. Stat. Med., 21, 1539-1558.
95. Monsees, G.M., Tamimi, R.M. and Kraft, P. (2009) Genome-wide association scans for secondary traits using case-control samples. Genet. Epidemiol. Epub ahead of print.
96. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J. et al. (2007) PLINK: A tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet., 81, 559-575.
97. Crane, A.M., Martin, L.S., Valle, D. and Ledley, F.D. (1992) Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase. Hum. Genet., 89, 259-264.
98. Crane, A.M., Jansen, R., Andrews, E.R. and Ledley, F.D. (1992) Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria. J. Clin. Invest., 89, 385-391.